Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Exp Cell Res. 2018 Mar 15;364(2):234-242. doi: 10.1016/j.yexcr.2018.02.015. Epub 2018 Feb 16.
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases. A balance of Rac1 and Cdc42 activity as well as proper microtubule organization and endoplasmic reticulum structure, are required to position the actin cluster. Further, ND proteins Sns and Duf also localize to this cluster and regulate organization of the actin and microtubule cytoskeleton. Perturbation of any of these inter-dependent components impairs nephrocyte ultrafiltration. Thus cytoskeletal components, Rho-GTPases and ND proteins work in concert to maintain the specialized nephrocyte architecture and function.
昆虫肾细胞为肾脏疾病提供了一个有价值的模型，因为它们在结构和功能上与哺乳动物的肾足细胞同源。它们具有一种特殊的大分子组装体，即肾细胞隔膜（ND），它作为过滤屏障，通过过滤废物和有毒产物来帮助维持组织内稳态。然而，维持肾细胞结构和 ND 的元素尚不清楚。我们发现果蝇肾细胞具有独特的细胞质 F-肌动蛋白簇，该簇由微管细胞骨架和 Rho-GTPases 维持。Rac1 和 Cdc42 活性的平衡以及适当的微管组织和内质网结构对于定位肌动蛋白簇是必需的。此外，ND 蛋白 Sns 和 Duf 也定位于该簇，调节肌动蛋白和微管细胞骨架的组织。这些相互依赖的成分中的任何一个受到干扰都会损害肾细胞的超滤功能。因此，细胞骨架成分、Rho-GTPases 和 ND 蛋白协同作用以维持特殊的肾细胞结构和功能。
